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Pharmacophore-Directed Retrosynthesis Applied to Ophiobolin A: Simplified Bicyclic Derivatives Displaying Anticancer Activity.

ABSTRACT: Pharmacophore-directed retrosynthesis applied to ophiobolin A led to bicyclic derivatives that were synthesized and display anticancer activity. Key features of the ultimate defensive synthetic strategy include a Michael addition/facially selective protonation sequence to set the critical C6 stereocenter and a ring-closing metathesis to form the cyclooctene. Cytotoxicity assays toward a breast cancer cell line (MDA-MB-231) confirm the anticipated importance of structural complexity for selectivity (vs MCF10A cells) while C3 variations modulate stability.

SUBMITTER: Tao Y

PROVIDER: S-EPMC7655722 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Pharmacophore-Directed Retrosynthesis Applied to Ophiobolin A: Simplified Bicyclic Derivatives Displaying Anticancer Activity.

Tao Yongfeng Y Reisenauer Keighley N KN Masi Marco M Evidente Antonio A Taube Joseph H JH Romo Daniel D

Organic letters 20201009 21

Pharmacophore-directed retrosynthesis applied to ophiobolin A led to bicyclic derivatives that were synthesized and display anticancer activity. Key features of the ultimate defensive synthetic strategy include a Michael addition/facially selective protonation sequence to set the critical C6 stereocenter and a ring-closing metathesis to form the cyclooctene. Cytotoxicity assays toward a breast cancer cell line (MDA-MB-231) confirm the anticipated importance of structural complexity for selectivi ...[more]

PMID: 33034457

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